Research Interests

Hepatitis C virus (HCV) infects over 170 million individuals worldwide and often leads to chronic liver diseases, including chronic hepatitis C, cirrhosis and hepatocellular carcinoma. There is as yet no vaccine for hepatitis C. microRNAs (miRNAs) are small non-coding RNAs (~22 nt) that regulate gene expression primarily through post-transcriptional destabilization, translational repression of target mRNAs which bear complementary sites, or a combination of these two mechanisms. miRNAs are likely to play significant roles in HCV replication and the development and progression of HCV-induced liver diseases. Dr. Hou is interested in understanding roles of miRNAs and other non-coding RNAs (ncRNAs) in the pathogenesis of hepatitis C and HCV-induced liver diseases, and developing new therapies to combat HCV and HCV-associated liver diseases. Dr. Hou and colleagues have shown that miRNA-196 plays a role in the regulation of HCV replication and infection in HCV replicon and infectious cell culture systems. miR-196 may hold promise as a potential novel strategy to prevent or ameliorate hepatitis C infection, and to protect against liver injury in chronic HCV infection.

Dr. Hou’s other areas of special interest are hepatic heme and porphyrin metabolism. Heme oxygenase-1 (HMOX1) is the initial and rate-controlling enzyme involved in heme degradation to biliverdin, carbon monoxide and ferrous iron. HMOX1, one of key cytoprotective enzymes, has anti-oxidative and anti-inflammatory activities. Bach1, a basic leucine zipper mammalian transcriptional repressor, negatively regulates HMOX1. The evidence is clear that oxidative stress occurs in chronic liver diseases. The goal of this ongoing project is to elucidate the molecular mechanism underlying the regulation of HMOX1/Bach1, and to develop therapeutic agents for treatment of chronic liver diseases. Dr. Hou and colleagues have identified and validated a number of miRNAs, including the let-7 miRNA family and miRNA-196, which enhance HMOX1 gene expression through direct translational repression of Bach1. Furthermore, they have demonstrated that over-expression of those miRNAs attenuates oxidant injury in human hepatocytes. The study has revealed, for the first time, a new role of the let-7 microRNA family in modulation of HMOX1. The results may also have implications for a novel approach to protecting hepatocytes from oxidant injury, which is known to accelerate the progression of hepatitis, liver fibrosis and other forms of liver disease.